Application of high-performance liquid chromatography and thermospray high-performance liquid chromatography-mass spectrometry to the analysis and identification of 2',3'-dideoxyadenosine and its metabolite in biological media

Reversed-phase high-performance liquid chromatographic (HPLC) procedures are described for determining the stability of 2',3'-dideoxyadenosine (DDA) in biological fluids at therapeutic dosages. The validated methodology uses both direct injection and solid-phase extraction techniques. Deamination of DDA to 2',3'-dideoxyinosine (DDI) in plasma by adenosine deaminase was monitored by HPLC, and the identification of DDI verified by thermospray HPLC-mass spectrometry. This methodology should prove useful in future studies concerning the stability and metabolism of dideoxynucleosides.     

Formation and sigmatropic rearrangement of PhCOC(NO2)CH2 cycloadducts of 1,3-cyclohexadiene: a theoretical study

Competing cycloaddition pathways for the reaction of 2-nitro-1-phenyl-2-propen-1-one with 1,3-cyclohexadiene were investigated employing computational methods. A bifurcating pathway was found for formation of nitroketone 3 and nitronic ester 5. A second bifurcating pathway was found for the formation of nitroketone 4 and enol ether 6. Sigmatropic rearrangements of two cycloadducts, nitronic ester 5 and enol ether 6, were also studied computationally. The reaction pathways were mapped using the B3-LYP/6-311G(d) method and relative energies for species 3-6 were calculated at the same level. Solution-phase corrections were performed by the PCM method. The calculations for both bifurcating cycloaddition pathways indicate kinetic control with similar rate-determining activation energies. The nitroketone 3 is more stable than nitronic ester 5 by 5.3 kcal/mol and nitroketone 4 is more stable than enol ether 6 by 3.9 kcal/mol, consistent with the observed direction of sigmatropic rearrangement.     

Bacterial growth response to photoactive quinones

Quinones are known producers of reactive oxygen species (ROS) that may be toxic in natural aquatic environments. In this study, the effects of parent quinones and their photodegradation products on bacterial growth were determined, and photochemical ROS formation rates were measured. Using (3)H-leucine incorporation to measure growth of the bacterium Pseudomonas aeruginosa and natural seawater bacterioplankton, growth inhibition was observed when samples were exposed to dichlone, chloranil and sodium anthraquinone-2-sulfonate (AQ2S). For seawater, compared with other quinones tested, dichlone showed the greatest toxicity in the dark, and AQ2S toxicity was greatest during simultaneous exposure to sunlight. Photodegraded chloranil and dichlone showed decreased toxicity compared with nonirradiated samples. For P. aeruginosa, AQ2S and its photodegradation products showed the greatest toxicity during simultaneous exposure to sunlight. Chloranil photodegradation products showed reduced toxicity compared with the parent compound during simultaneous exposure to sunlight. Dichlone was the only compound to show any toxicity to P. aeruginosa in the dark, and its photodegradation products were more toxic than the parent compound. Based on the results of dark and light controlled experiments measuring bacterial growth and estimated ROS production rates, ROS alone does not account for relative differences in toxicity between these quinones.     

Non-homogeneous random walks on a semi-infinite strip

We study the asymptotic behaviour of Markov chains (_Xn,_ηn)$(X_n,{\eta }_n)$ on _Z+×S${\mathbb{Z}}_{+}\times S$, where _Z+${\mathbb{Z}}_{+}$ is the non-negative integers and S$S$ is a finite set. Neither coordinate is assumed to be Markov. We assume a moments bound on the jumps of _Xn$X_n$, and that, roughly speaking, _ηn${\eta }_n$ is close to being Markov when _Xn$X_n$ is large. This departure from much of the literature, which assumes that _ηn${\eta }_n$ is itself a Markov chain, enables us to probe precisely the recurrence phase transitions by assuming asymptotically zero drift for _Xn$X_n$ given _ηn${\eta }_n$. We give a recurrence classification in terms of increment moment parameters for _Xn$X_n$ and the stationary distribution for the large- X$X$ limit of _ηn${\eta }_n$. In the null case we also provide a weak convergence result, which demonstrates a form of asymptotic independence between _Xn$X_n$ (rescaled) and _ηn${\eta }_n$. Our results can be seen as generalizations of Lamperti’s results for non-homogeneous random walks on _Z+${\mathbb{Z}}_{+}$ (the case where S$S$ is a singleton). Motivation arises from modulated queues or processes with hidden variables where _ηn${\eta }_n$ tracks an internal state of the system.     

Synthesis and cross coupling of a highly substituted 2-pyridylboronate: application to the large scale synthesis of a mineralocorticoid antagonist

The large scale synthesis of functionalized 2-pyridylboronate 8 and optimization of its Suzuki-Miyaura coupling to chloropyrazoline (R)-7 to provide a scalable synthesis of mineralocorticoid antagonist (R)-1 is described.     

A bargaining game model for measuring performance of two-stage network structures

Data envelopment analysis (DEA) is a method for measuring the efficiency of peer decision making units (DMUs), where the internal structures of DMUs are treated as a black-box. Recently DEA has been extended to examine the efficiency of DMUs that have two-stage network structures or processes, where all the outputs from the first stage are intermediate measures that make up the inputs to the second stage. The resulting two-stage DEA model not only provides an overall efficiency score for the entire process, but also yields an efficiency score for each of the individual stages. The current paper develops a Nash bargaining game model to measure the performance of DMUs that have a two-stage structure. Under Nash bargaining theory, the two stages are viewed as players and the DEA efficiency model is a cooperative game model. It is shown that when only one intermediate measure exists between the two stages, our newly developed Nash bargaining game approach yields the same results as applying the standard DEA approach to each stage separately. Two real world data sets are used to demonstrate our bargaining game model.     

Synthesis, structure, and properties of a T-shaped 14-electron stiboranyl-gold complex

A cyclic stiboranyl-gold complex (1) supported by two 1,8-naphthalenediyl linkers has been synthesized and structurally characterized. The gold atom of this complex adopts a T-shaped geometry and is separated from the antimony center by only 2.76 ?. Surprisingly, the trivalent gold atom of this complex is involved in an aurophilic interaction, a phenomenon typically only observed for monovalent gold complexes. This phenomenon indicates that the stiboranyl ligand possesses strong σ-donating properties making the trivalent gold atom of 1 electron rich. This view is supported by DFT calculations as well as Au L(3)- and Sb K-edge XANES spectra which reveal that 1 may also be described as an aurate-stibonium derivative. In agreement with this view, complex 1 shows no reactivity toward the halides Cl(-), Br(-), and I(-). It does, however, rapidly react with F(-) to form an unprecedented anionic aurate fluorostiborane complex ([2](-)) which has been isolated as the tetra-n-butylammonium salt. The increased coordination number of the antimony center in this anionic complex ([2](-)) does not notably affect the Au-Sb separation (2.77 ?) or the geometry at the gold atom which remains T-shaped.     

Infrared emission following photolysis of methylisothiocyanate and methylthiocyanate

Methylisothiocyanate (CH(3)NCS) was photolyzed at 193 and 248 nm, and the resulting time-resolved infrared emission was observed. Similar experiments were performed on methylthiocyanate (CH(3)SCN) photolyzed at 193 nm. Previous work suggested that these isomers undergo excited-state isomerization prior to dissociation, but other experiments have contradicted this claim. In the infrared emission experiments, we observed the same products from both starting materials, supporting the theory of excited-state isomerization prior to dissociation. Methylisothiocyanate is the active ingredient in a widely used pesticide and has been observed to form highly toxic methyl isocyanate (CH(3)NCO) under environmental conditions. The mechanism for this formation has been unclear, but must involve some oxygen-containing species. At 248 nm, methylisothiocyanate was photolyzed alone and with three atmospheric oxidizers: O(2), NO, and NO(2). No chemical reaction was observed with O(2), whereas secondary reactions were observed with NO and NO(2). When methylisothiocyanate was photolyzed with NO(2), methyl isocyanate (CH(3)NCO) was observed, suggesting a likely environmental mechanism for methyl isocyanate formation.     

Processes limiting the rate of response in photorefractive composites

The processes limiting the rate of response of highly diffractive, reorientationally enhanced photorefractive polymer composite materials are identified from a series of degenerate four wave mixing and Mach–Zehnder interferometric measurements. In the regime of low intensity writing beams charge generation limits the rate of holographic grating formation, but at higher intensities charge transport or reorientation of dye molecules can restrict the rate of grating formation more strongly. A grating risetime of 540 ms is observed in a composite of high dye content with high reorientational mobility of the dye molecules. In this case it is proposed that the charge carrier mobility of the doped poly(N-vinylcarbazole):2,4,7-trinitro-9-fluorenone (PVK:TNF) matrix is the principal limiting factor in grating response rates.